The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people

被引：12

作者：

Shepherd, L. ^{[1
]}

Borges, A. H. ^{[2
]}

Harvey, R. ^{[3
,4
]}

Bower, M. ^{[5
]}

Grulich, A. ^{[6
]}

Silverberg, M. ^{[7
]}

Weber, J. ^{[8
]}

Ristola, M. ^{[9
,10
]}

Viard, J-P ^{[11
]}

Bogner, J. R. ^{[12
]}

Gargalianos-Kakolyris, P. ^{[13
,14
]}

Mussini, C. ^{[15
]}

Mansinho, K. ^{[16
]}

Yust, I. ^{[17
]}

Paduta, D. ^{[18
]}

Jilich, D. ^{[19
]}

Smiatacz, T. ^{[20
]}

Radoi, R. ^{[21
]}

Tomazic, J. ^{[22
]}

Plomgaard, P. ^{[23
]}

Frikke-Schmidt, R. ^{[23
]}

Lundgren, J. ^{[2
]}

Mocroft, A. ^{[1
]}

机构：

[1] UCL, Res Dept Infect & Populat Hlth, London, England

[2] Univ Copenhagen, Ctr Excellence Hlth Immun & Infect, Dept Infect Dis, Rigshosp, Copenhagen, Denmark

[3] Imperial Coll Healthcare Natl Hlth Serv Trust, Charing Cross Oncol Lab, Charing Cross Hosp Campus, London, England

[4] Imperial Coll Healthcare Natl Hlth Serv Trust, Trophoblast Dis Ctr, Charing Cross Hosp Campus, London, England

[5] Chelsea & Westminster Hosp NHS Fdn Trust, Natl Ctr HIV Malignancy, London, England

[6] Univ New South Wales, Kirby Inst, Sydney, NSW, Australia

[7] Kaiser Permanente Northern Calif, Oakland, CA USA

[8] Imperial Coll London, London, England

[9] Univ Helsinki, Div Infect Dis, Helsinki, Finland

[10] Helsinki Univ Hosp, Helsinki, Finland

[11] Hop Hotel Dieu, AP HP, Diagnost & Therapeut Ctr, Paris, France

[12] Univ Munich, Dept Internal Med 4, Munich, Germany

[13] Gen Hosp Athens G Gennimatas, Dept Internal Med 1, Athens, Greece

[14] Gen Hosp Athens G Gennimatas, Infect Dis Unit, Athens, Greece

[15] Univ Modena & Reggio Emilia, Clin Infect & Trop Dis, Azienda Policlin, Modena, Italy

[16] Hosp Egas Moniz CHLO, Dept Infect Dis, EPE, Lisbon, Portugal

[17] Ichilov Hosp, Tel Aviv, Israel

[18] Gomel Reg Ctr Hyg, Gomel, BELARUS

[19] Charles Univ Prague, Fac Med 1, Dept Infect & Trop Dis, Prague, Czech Republic

[20] Med Univ Gdansk, Dept Infect Dis, Gdansk, Poland

[21] Clin Hosp Infect & Trop Dis Dr Victor Babes, Bucharest, Romania

[22] Univ Med Ctr Ljubljana, Dept Infect Dis, Ljubljana, Slovenia

[23] Rigshosp, Dept Clin Biochem, Copenhagen, Denmark

来源：

HIV MEDICINE | 2018年 / 19卷 / 02期

基金：

新加坡国家研究基金会; 瑞士国家科学基金会;

关键词：

B-cell dysfunction; biomarkers; free light chains; HIV; immunoglobulins; lymphoma; FREE LIGHT-CHAINS; NON-HODGKIN-LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; CANCER-RISK; UNITED-STATES; AIDS; INFECTION; IMMUNODEFICIENCY; INFLAMMATION; STIMULATION;

D O I：

10.1111/hiv.12546

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

ObjectivesB-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-, FLC-, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people. MethodsA nested matched case-control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls. Markers of B-cell dysfunction were measured in prospectively stored serial plasma samples collected before the diagnosis of lymphoma (or selection date in controls). Marker levels 2 and > 2 years prior to diagnosis were investigated. ResultsTwo-fold higher levels of FLC- [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.19, 2.84], FLC- (OR 2.15; 95% CI 1.34, 3.46), IgG (OR 3.05; 95% CI 1.41, 6.59) and IgM (OR 1.46; 95% CI 1.01, 2.11) were associated with increased risk of lymphoma > 2 years prior to diagnosis, but not 2 years prior. Despite significant associations > 2 years prior to diagnosis, the predictive accuracy of each marker was poor, with FLC- emerging as the strongest candidate with a c-statistic of 0.67 (95% CI 0.58, 0.76). ConclusionsFLC-, FLC- and IgG levels were higher > 2 years before lymphoma diagnosis, suggesting that B-cell dysfunction occurs many years prior to lymphoma development. However, the predictive value of each marker was low and they are unlikely candidates for risk assessment for targeted intervention.

引用

页码：90 / 101

页数：12

共 41 条

[1] Immune activation and inflammation in HIV-I infection: causes and consequences [J].